FAME. Some familial epilepsy syndromes are notoriously resistant to gene discovery. Familial Adult Myoclonus Epilepsy (FAME), a rare but distinct familial epilepsy, has been one of the familial epilepsy syndromes that has been around for more than a decade. Despite the power of modern massive parallel sequencing technologies, this syndrome has been hard to tackle. In a recent publication, we take a small step in narrowing down the region for the FAME gene. Let’s use this opportunity for a reality check of the somewhat disappointing state of gene discovery in familial epilepsies in 2016 and what we can do about this. Continue reading
Monthly Archives: July 2016
Misusing the concept of epileptic encephalopathy – on purpose
EEs. The concept of epileptic encephalopathy refers to a process where epileptic activity impairs overall brain function, including cognitive function, language, and behavior. In a recent commentary in Epilepsia, our current use and misuse of the concept of epileptic encephalopathy is reviewed critically. In summary, the authors criticize that epileptic encephalopathy is used as a diagnostic category rather than a description of the actual epileptic process, suggesting that another term may be necessary for the group of patients with intellectual disability and epilepsy where we often find a genetic etiology. In this blog post, I would like to plead guilty on behalf of the epilepsy genetics community for having misused the concept of epileptic encephalopathies for almost a decade. And we have done this for at least three different reasons. Continue reading
Where the genes have no names – KIAA2022 in epileptic encephalopathy
No name. The speed of gene discovery in human epilepsies is sometimes so fast that genetics beats biology. Some genes are implicated in disease faster than our ability to name them. In a recent publication, we describe the epilepsy phenotype of an X-linked gene that is only known by an identifier that indicates how little we know about it: KIAA2022. In contrast to a phenotype in males that is mainly characterized by intellectual disability, de novo mutations in KIAA2022 in females results in intractable myoclonic epilepsy. Continue reading
RORB in generalized epilepsy with absences – going retinoic
Retinoic receptor. A few years ago, when exome sequencing was still in its infancy, our group in Kiel identified a small de novo in frame deletion in a gene that we didn’t know how to interpret. In frame deletions that do not disturb the reading frame, but simply take one or several amino acids out, are usually less suspicious and are sometimes even filtered out by the algorithms that we and others typically use. We dismissed this finding for several years. However, a year ago, the plot thickened when other groups mentioned that they had found the same gene in their patients, including a family with six affected individuals. In a recent publication, we describe the improbable story of RORB, the latest gene for generalized epilepsies with prominent photosensitivity and absence seizures. Continue reading